Management of Non–ST-Elevation Myocardial Infarction: The Bright Gleam of Progress, but Much Work Remains

TLDR: Whether the trend of decreasing mortality has continued in the last decade is sought and the relative contributions of changing comorbid status, clinical risk profile at presentation, and acute medical and interventional treatments to changing outcomes in patients with NSTEMI are examined.

Abstract: Cardiovascular disease remains the largest contributor to global mortality, accounting for nearly half of the 36 million annual deaths from noncommunicable diseases, making it a major priority for global health policy initiatives.1,2 In developed countries, mortality due to cardiovascular disease has declined approximately 50% to 80% during the late 20th and early 21st centuries.3 This success story is most certainly multifactorial. The last several decades have witnessed substantial advances in the understanding of the causative factors and pathophysiology underlying vascular disease, allowing for targeted approaches to risk factor reduction for primary prevention (eg, blood pressure and cholesterol control) as well as effective strategies for management of acute events and for secondary prevention of recurrent events. Incremental benefit was seen even during the last decade with the introduction of risk stratification tools to guide decisions regarding early invasive coronary strategies, more potent antiplatelet therapies, and improved drug-eluting stent technologies.4-6 As such, it appears that there has been both a reduction in the incidence of cardiovascular events and a decrease in event-related fatality rates. For example, the WHO MONICA study of predominantly high-income countries reported a 4% annual decline in death rates due to coronary heart disease. Approximately 75% of the decrease was attributed to a reduction in coronary event rates, reflecting risk factor modification, and the remainder was due to a decrease in case-fatality rates related to improvements in acute medical and secondary preventive therapy.7 Randomized trials are the source of robust evidence for the benefit of and interplay between pharmacological treatments and invasive coronary strategies in managing acute coronary syndrome.4,5 After incorporation of these therapies into guidelines, investigators typically use registries to describe adherence to guideline-based treatments and to ascertain whether adherence is associated with changes in outcomes in the community. For example, a study of the Global Registry of Acute Coronary Events (GRACE) registry between 1999 and 2006 found that use of guideline-recommended treatments such as acute pharmacotherapy (eg, β-blockers, statins, and thienopyridines) and percutaneous coronary intervention (PCI) increased significantly among patients with non–ST-elevation myocardial infarction (NSTEMI); taken together, these changes were associated with a 33% riskadjusted decrease in death (from 4.9% to 3.3%) at 6 months.8 Despite several studies evaluating the association between adherence to guideline-based strategies and outcomes, the relative importance of the individual therapies (eg, invasive coronary approach vs pharmacotherapies) and the clinical context of the health care system in which they are applied are less clear. In a related article in JAMA, Hall and colleagues utilized the size and scope of the Myocardial Ischemia National Audit Project (MINAP) database, a national registry of patients with acute coronary syndrome admitted in England and Wales, to investigate the trends in risk profile, treatments, and outcomes among 389 057 patients presenting with NSTEMI between 2003 and 2013.9,10 Specifically, the authors sought to determine whether the trend of decreasing mortality has continued in the last decade and to examine the relative contributions of changing comorbid status, clinical risk profile at presentation, and acute medical and interventional treatments to changing outcomes in patients with NSTEMI. Hall and colleagues describe a 30% relative decrease in unadjusted 6-month all-cause mortality from 10.8% in 2003 to 7.6% in 2013. During this time, there was an increase in the prevalence of many comorbidities, including diabetes, hypertension, emphysema, renal failure, and smoking, but a decline in clinical risk of mortality at the time of acute coronary syndrome presentation as defined by the GRACE risk score (which incorporates age, cardiac arrest, ST-segment deviation, biomarker elevation, blood pressure, heart rate, heart failure, and renal function). Individuals defined as intermediate to high risk (GRACE score ≥88) represented the majority of patients throughout the study period, but with a significant decline in the proportion of patients in this risk group over time (87.2% in 2003-2004 to 82.0% in 2012-2013; P = .01). Adherence to guideline-based therapy was high throughout, with a significant increase in adherence during the 10-year study period. Notably, an invasive coronary strategy, defined as coronary angiography, PCI, or coronary artery bypass graft (CABG) surgery, increased from 42.7% to 78.6% over the course of the study (P < .001). Although the rates of CABG appeared relatively constant at less than 5%, the rates of PCI increased from less than 10% to 33% over time, which consistently represented approximately half of the patients who underwent coronary angiography. Hall and colleagues drew several important conclusions. First, the reduction in mortality persisted after adjustment for (1) the lower clinical risk at presentation as determined by the GRACE risk score; (2) the small but significant improvements in socioeconomic status (as measured by the Index of Multiple Deprivation); and (3) an increasing burden of Related article Opinion